Abstract
Five tacrine-ferulic acid hybrids (6a-e) were designed and synthesized as multi-potent anti-Alzheimer drug candidates. All target compounds have better acetylcholinesterase inhibitory activity and comparable butyrylcholinesterase inhibitory activity in relation to tacrine. Interestingly, 6d showed a reversible and non-competitive inhibitory action for acetylcholinesterase indicating interaction with the peripheral anionic site, whereas a reversible but competitive inhibitory action for butyrylcholinesterase. The antioxidant study revealed that four target compounds have, compared to Trolox, high ability to absorb reactive oxygen species.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholinesterase / drug effects*
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Acetylcholinesterase / metabolism
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Alzheimer Disease / drug therapy
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Antioxidants / pharmacology
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Binding Sites
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Butyrylcholinesterase / metabolism
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Cholinesterase Inhibitors / chemical synthesis
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Cholinesterase Inhibitors / pharmacology*
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Chromans / pharmacology
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Coumaric Acids / chemical synthesis
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Coumaric Acids / pharmacology*
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Drug Design*
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Humans
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Models, Chemical
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Reactive Oxygen Species / metabolism
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Structure-Activity Relationship
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Tacrine / analogs & derivatives
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Tacrine / chemical synthesis
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Tacrine / pharmacology*
Substances
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Antioxidants
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Cholinesterase Inhibitors
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Chromans
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Coumaric Acids
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Reactive Oxygen Species
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Tacrine
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ferulic acid
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Acetylcholinesterase
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Butyrylcholinesterase
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6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid